Hepatology Commons^™

Measuring Quality Of Life In Advanced Chronic Liver Disease With Fact-Hep: Findings From The Pal Liver Trial, Manisha Verma, Binu John, Don Rockey, Sid Barritt, Victor Navarro, Linda Shaw, Andrzej Kosinski, Elliot Tapper, Archita Desai

Einstein Health Papers

BACKGROUND: Patient-reported outcome measures (PROMs) are increasingly incorporated into hepatology research, yet few have been rigorously evaluated, particularly among patients with decompensated cirrhosis. The Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) captures multidimensional liver disease-specific burden, while the disease-agnostic PROMIS-29 assesses physical and mental health broadly. We evaluated the performance of FACT-Hep and its relationship to PROMIS-29 among participants with cirrhosis or hepatocellular carcinoma (HCC) enrolled in a prospective multicenter clinical trial.

METHODS: Baseline data were analyzed from 935 participants enrolled in the PAL LIVER trial. This study enrolled patients with Child-Turcotte-Pugh (CTP) B/C cirrhosis and/or with HCC. Health-related quality of …

The Transitional Liver Clinic: Study Protocol For A Stepped-Wedge Cluster Randomized Trial, Lindsay Yoder, Elliot B. Tapper, Richard S. Kalman, Mary Rinella, Nicole Bendin, Manisha Verma, Francis Pike, Naga Chalasani, Neha Nalumasu, Eric S. Orman

Einstein Health Papers

BACKGROUND: Patients with complications of advanced liver disease experience high rates of hospital readmission after discharge. Transitional care models have improved outcomes in other chronic conditions, but their efficacy in liver disease care remains uncertain. This randomized trial evaluates the effectiveness of a tailored transitional care model-the Transitional Liver Clinic (TLC)-in reducing readmissions, improving quality of life, and enhancing patient satisfaction for patients with advanced liver disease.

METHODS: This is a 45-month, stepped-wedge cluster randomized trial enrolling up to 1000 patients with advanced liver disease across 4 academic medical centers. Each site transitions from usual care to the TLC intervention …

Modeling The Impact Of Mmr Vaccination Strategies On Measles Outbreaks In Texas, Kaiming Bi, Thuy Nguyen, Boya Peng, Trudy Krause, Cecilia Ganduglia Cazaban, Janelle Rios, Cici Bauer, Catherine Troisi, Eric Boerwinkle, Aanand D Naik

Faculty, Staff and Student Publications

No abstract provided.

Multicomponent Parenteral Lipid Emulsions Do Not Prevent Liver Injury In Neonatal Pigs With Obstructive Cholestasis, Greg Guthrie, Caitlin Vonderohe, Valeria Meléndez Hebib, Barbara Stoll, Douglas Burrin

Children’s Nutrition Research Center Staff Publications

Biliary atresia (BA) is a pediatric liver disease that often necessitates parenteral nutrition (PN) to support growth due to impaired liver function. While soy-based lipid emulsions (SLE) are commonly used in PN, they may contribute to cholestatic liver injury. In contrast, mixed lipid emulsions (MLE) show promise in preventing cholestasis in infants without BA, potentially by restoring bile flow. However, their effectiveness in patients of complete bile duct obstruction, as seen in BA, remains uncertain. To explore the potential benefits of MLE in BA, we utilized a neonatal pig model of bile duct ligation (BDL). Pigs underwent either BDL or …

Factors Driving Adolescent Tuberculosis Incidence By Age And Sex In 30 High-Tuberculosis Burden Countries: A Mathematical Modelling Study, Silvia S Chiang, Megan B Murray, Alexander W Kay, Peter J Dodd

Faculty, Staff and Students Publications

INTRODUCTION: During adolescence, tuberculosis incidence rises, with a greater increase in males compared with females. Tuberculosis notifications and estimates infrequently disaggregate adolescent age groups. Moreover, the factors that drive the increases in overall incidence and the male-to-female (MF) ratio remain unclear.

METHODS: We constructed a mechanistic model to estimate cumulative Mycobacterium tuberculosis infection and tuberculosis disease incidence in the WHO’s 30 high-tuberculosis burden countries (HBCs), which represent 86%–90% of global tuberculosis incidence. We derived infection risk from tuberculosis prevalence and assortative social mixing based on sex and age (10–14 years vs 15–19 years old). We adjusted age subgroup-specific risks of …

Phase 3 Validation Of Paam For Hepatocellular Carcinoma Risk Stratification In Cirrhosis, Naoto Fujiwara, Camden Lopez, Tracey L Marsh, Indu Raman, Cesia A Marquez, Subhojit Paul, Sumit K Mishra, Naoto Kubota, Courtney Katz, Hiroaki Kanzaki, Michael Gonzalez, Lisa Quirk, Sneha Deodhar, Pratibha Selvakumar, Prithvi Raj, Neehar D Parikh, Lewis R Roberts, Myron E Schwartz, Mindie H Nguyen, Alex S Befeler, Stephanie Page-Lester, Sudhir Srivastava, Ziding Feng, K Rajender Reddy, Saira Khaderi, Sumeet K Asrani, Fasiha Kanwal, Hashem B El-Serag, Jorge A Marrero, Amit G Singal, Yujin Hoshida

Faculty, Staff and Students Publications

Background & aims: Hepatocellular carcinoma (HCC) risk stratification is an urgent unmet need for cost-effective HCC screening and early detection in patients with cirrhosis to improve poor HCC prognosis.

Methods: Molecular (prognostic liver secretome signature with α-fetoprotein) and clinical (aMAP [age, male sex, albumin-bilirubin, and platelets] score) variable-based scores were integrated into PAaM (prognostic liver secretome signature with α-fetoprotein plus age, male sex, albumin-bilirubin, and platelets), which was subsequently validated in 2 phase 3 biomarker validation studies: the statewide Texas HCC Consortium and nationwide HCC Early Detection Strategy prospective cohorts, following the prospective specimen collection, retrospective blinded evaluation design. The …

Dairy Consumption And The Colonic Mucosa-Associated Gut Microbiota In Humans-A Preliminary Investigation, Ellie Chen, Nadim J Ajami, Donna L White, Yanhong Liu, Shawn Gurwara, Kristi Hoffman, David Y Graham, Hashem B El-Serag, Joseph F Petrosino, Li Jiao

Faculty, Staff and Students Publications

Background: Dairy consumption has been associated with various health outcomes that may be mediated by changes in gut microbiota.

Methods: This cross-sectional study investigated the association between the colonic mucosa-associated gut microbiota and the self-reported intake of total dairy, milk, cheese, and yogurt. A total of 97 colonic mucosal biopsies collected from 34 polyp-free individuals were analyzed. Dairy consumption in the past year was assessed using a food frequency questionnaire. The 16S rRNA gene V4 region was amplified and sequenced. Operational taxonomic unit (OTU) classification was performed using the UPARSE and SILVA databases. OTU diversity and relative abundance were compared …

Hes V20 Outperforms Galad For Detection Of Hcc: A Phase 3 Biomarker Study In The United States, Hashem B El-Serag, Qingchun Jin, Nabihah Tayob, Emad Salem, Michelle Luster, Abeer Alsarraj, Saira Khaderi, Amit G Singal, Jorge A Marrero, Sumeet K Asrani, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: The original hepatocellular carcinoma early detection screening (HES) score, which combines alpha-fetoprotein (AFP) with age, alanine aminotransferase, and platelets, has better performance than AFP alone for early HCC detection. We have developed HES V2.0 by adding AFP-L3 and des-gamma-carboxy prothrombin to the score and compared its performance to GALAD and ASAP scores among patients with cirrhosis.

APPROACH AND RESULTS: We conducted a prospective-specimen collection, retrospective-blinded-evaluation phase 3 biomarker cohort study in patients with cirrhosis enrolled in imaging and AFP surveillance. True-positive rate (TPR)/sensitivity and false-positive rate for any or early HCC were calculated for GALAD, ASAP, and …

Defining Renal Recovery In Patients With Hepatorenal Syndrome-Acute Kidney Injury: Experience From North American Studies, Muhammad A. Mujtaba, Hussien Elsiesy, Sara Faiz, Syed A. Hussain, Ann Kathleen N. Gamilla-Crudo, Aftab Karim, Mohammad I. Khan, Muhammad W. Khattak, Zunaira Zafar, Michael Kueht, Khurram Jamil

Jefferson Health - Northeast Papers (formerly Aria Health Papers)

INTRODUCTION: The degree of improvement in serum creatinine (SCr) has previously been suggested as a sensitive indicator of treatment response in patients with hepatorenal syndrome-acute kidney injury (HRS-AKI), while HRS reversal remains the primary endpoint in clinical trials.

METHODS: A total of ≥ 30% SCr improvement was analyzed as an exploratory prespecified endpoint in the CONFIRM trial. In this post hoc analysis, intent-to-treat population data from three Phase 3 studies (OT-0401, REVERSE, and CONFIRM) conducted in North America in patients with HRS-AKI were pooled to assess the incidence of > 30% improvement in SCr and its association with clinical outcomes.

RESULTS: …

Impact Of Racial, Ethnic, And Socioeconomic Disparities On Presentation And Survival Of Hcc: A Multicenter Study, Nicole E Rich, Patricia D Jones, Hong Zhu, Tanushree Prasad, Amy Hughes, Sandi Pruitt, Caitlin C Murphy, Karim Seif-El-Dahan, Darine Daher, Gloria Figueroa, Stephanie Castaneda, Lisa Quirk, Michael Gonzales, Osiris Carranza, Samantha Bourque, Nargis Baset, Adam C Yopp, Amit G Singal

Faculty, Staff and Student Publications

BACKGROUND: Racial and ethnic disparities have been reported for HCC prognosis, although few studies fully account for clinically important factors and social determinants of health, including neighborhood socioeconomic status.

METHODS: We conducted a retrospective multicenter cohort study of patients newly diagnosed with HCC from January 2010 through August 2018 at 4 large health systems in the United States. We used multivariable logistic regression and cause-specific Cox proportional hazard models to identify factors associated with early-stage HCC presentation and overall survival.

RESULTS: Of 2263 patients with HCC (37.6% non-Hispanic White, 23.5% non-Hispanic Black, 32.6% Hispanic, and 6.4% Asian/other), 42.0% of patients …

Serum Levels Of Total Bile Acids Are Associated With An Increased Risk Of Hcc In Patients With Cirrhosis, Hashem B El-Serag, Aaron P Thrift, Hao Duong, Jing Ning, Saira Khaderi, Amit G Singal, Sumeet K Asrani, Jorge A Marrero, Hannah Powell, Kinza Rizwan, Omar Najjar, Christopher I Amos, Michelle Luster, Abeer Al-Sarraj, Emad Salem, Michael E Scheurer, Jagpreet Chhatwal, Salma Kaochar, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND: Previous studies have reported higher circulating bile acid levels in patients with HCC compared to healthy controls. However, the association between prediagnostic bile acid levels and HCC risk among patients with cirrhosis is unclear.

METHODS: We measured total BA (TBA) concentration in serum samples collected from a prospective cohort of patients with cirrhosis who were followed until the development of HCC, death, or last study date. Competing risk proportional hazard-adjusted models were used to estimate the association between tertiles of serum TBA levels and the risk of developing HCC. We quantified the incremental predictive value of serum bile acid …

Glp-1 Receptor Agonists And Risk For Cirrhosis And Related Complications In Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease, Fasiha Kanwal, Jennifer R Kramer, Liang Li, Yu-Xiao Yang, Yumei Cao, Xian Yu, Ronald Samuel, Basim Ali, Roxanne Desiderio, George Cholankeril, Mandeep Bajaj, Hashem B El-Serag, Steven M Asch

Faculty, Staff and Students Publications

IMPORTANCE: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an increasing cause of cirrhosis. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are effective in improving liver inflammation in patients with MASLD.

OBJECTIVE: To determine whether use of GLP-1 RAs is associated with lower risk of developing cirrhosis and its complications, including decompensation and hepatocellular cancer (HCC), among patients with MASLD.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study with an active comparator, new-user design used data from the national Veterans Health Administration Corporate Data Warehouse and Central Cancer Registry. Patients with MASLD and diabetes who were seen at 130 Veterans Health …

Neighborhood-Level Deprivation Mediates Racial And Ethnic Disparities In Hcc Diagnosis In Texas, Itunu O Sokale, Aaron P Thrift, Hashem B El-Serag, Abiodun O Oluyomi

Faculty, Staff and Students Publications

BACKGROUND: Texas has the highest HCC rates in the United States, and the greatest burden is among Hispanics. Racial and ethnic disparities in HCC incidence have multiple underpinning factors. We conducted a mediation analysis to examine the role of neighborhood disadvantage (Area Deprivation Index) as a potential mediator of the association between neighborhood race and ethnicity distribution and neighborhood HCC case counts in Texas.

METHODS: The primary outcome measure was counts of new HCC diagnoses per census tract based on Texas Department of State Health Services Texas Cancer Registry data. The primary exposure of interest was the race and ethnicity-based …

Genomic Biomarkers To Predict Response To Atezolizumab Plus Bevacizumab Immunotherapy In Hepatocellular Carcinoma: Insights From The Imbrave150 Trial, Sun Young Yim, Sung Hwan Lee, Seung-Woo Baek, Bohwa Sohn, Yun Seong Jeong, Sang-Hee Kang, Kena Park, Hyewon Park, Sunyoung S Lee, Ahmed O Kaseb, Young Nyun Park, Sun-Hee Leem, Michael A Curran, Ji Hoon Kim, Ju-Seog Lee

Faculty, Staff and Student Publications

Background/aims: Combination immunotherapy, exemplified by atezolizumab plus bevacizumab, has become the standard of care for inoperable hepatocellular carcinoma (HCC). However, the lack of predictive biomarkers and limited understanding of response mechanisms remain a challenge.

Methods: Using data from the IMbrave150plus cohort, we applied an immune signature score (ISS) predictor to stratify HCC patients treated with atezolizumab plus bevacizumab or with sorafenib alone into potential high and low response groups. By applying multiple statistical approaches including a Bayesian covariate prediction algorithm, we refined the signature to 10 key genes (ISS10) for clinical use while maintaining similar predictive power to the full …

Burden Of Mortality From Hepatocellular Carcinoma And Biliary Tract Cancers By Race And Ethnicity And Sex In Us, 2018–2023, Donghee Kim, Richie Manikat, Karn Wijarnpreecha, George Cholankeril, Aijaz Ahmed

Faculty, Staff and Students Publications

BACKGROUNDS/AIMS: The trends in mortality of hepatocellular carcinoma (HCC) and biliary tract cancers stratified by sex and race/ethnicity in the US continue to evolve. We estimated the sex- and race/ethnicity-based trends in HCC and biliary tract cancers-related mortality in US adults with a focus on disease burden.

METHODS: We performed a population-based analysis using the US national mortality records from 2018 to 2023. We identified HCC and biliary tract cancer using appropriate ICD-10 codes. Temporal trends in mortality were calculated by joinpoint analysis with annual percentage change (APC).

RESULTS: Annual age-standardized mortality from HCC decreased steadily with an APC of …

Gut Phageome In Mexican Americans: A Population At High Risk For Metabolic Dysfunction-Associated Steatotic Liver Disease And Diabetes, Suet-Ying Kwan, Caroline M Sabotta, Lorenzo R Cruz, Matthew C Wong, Nadim J Ajami, Joseph B Mccormick, Susan P Fisher-Hoch, Laura Beretta

Faculty, Staff and Student Publications

Mexican Americans are disproportionally affected by metabolic dysfunction-associated steatotic liver disease (MASLD), which often co-occurs with diabetes. Despite extensive evidence on the causative role of the gut microbiome in MASLD, studies determining the involvement of the gut phageome are scarce. In this cross-sectional study, we characterized the gut phageome in Mexican Americans of South Texas by stool shotgun metagenomic sequencing of 340 subjects, concurrently screened for liver steatosis by transient elastography. Inter-individual variations in the phageome were associated with gender, country of birth, diabetes, and liver steatosis. The phage signatures for diabetes and liver steatosis were subsequently determined. Enrichment of …

Facilitators And Barriers To Initiating And Completing Tuberculosis Preventive Treatment Among Children And Adolescents Living With Hiv In Uganda: A Qualitative Study Of Adolescents, Caretakers And Health Workers, Pauline Mary Amuge, Denis Ndekezi, Moses Mugerwa, Dickson Bbuye, Diana Antonia Rutebarika, Lubega Kizza, Christine Namugwanya, Angella Baita, Peter James Elyanu, Patricia Nahirya Ntege, Dithan Kiragga, Carol Birungi, Adeodata Rukyalekere Kekitiinwa, Agnes Kiragga, Moorine Peninah Sekadde, Nicole-Austin Salazar, Anna Maria Mandalakas, Philippa Musoke

Faculty, Staff and Students Publications

INTRODUCTION: People living with HIV (PLHIV) have a 20-fold risk of tuberculosis (TB) disease compared to HIV-negative people. In 2021, the uptake of TB preventive treatment among the children and adolescents living with HIV at the Baylor-Uganda HIV clinic was 45%, which was below the national target of 90%. Minimal evidence documents the enablers and barriers to TB preventive treatment (TPT) initiation and completion among children and adolescents living with HIV(CALHIV). We explored the facilitators and barriers to TPT initiation and completion among CALHIV among adolescents aged 10-19years and caretakers of children below 18years.

METHODS: We conducted a qualitative study …

In Utero Exposure To Antihistamines And Risk Of Hepatocellular Carcinoma In A Multigenerational Cohort, Caitlin C Murphy, Karim Seif El Dahan, Amit G Singal, Piera M Cirillo, Nickilou Y Krigbaum, Barbara A Cohn

Faculty, Staff and Student Publications

BACKGROUND: Growing evidence suggests that liver disease originates in early life. Antihistamines cross the placenta and are frequently prescribed to pregnant women to treat nausea and vomiting, as well as allergy and asthma symptoms. Exposure to antihistamines in utero may impact the developing liver by reprogramming or inducing epigenetic changes in fetal hepatocytes.

METHODS: We examined in utero exposure to antihistamines and the risk of HCC in the Child Health and Development Studies, a multigenerational cohort that enrolled pregnant women in the East Bay, CA, between 1959 and 1966 (n=14,507 mothers and 18,751 liveborn offspring). We reviewed mothers' medical records …

Low Vitamin D Levels In Patients With Symptoms Of Gastroparesis: Relationships With Nausea And Vomiting, Gastric Emptying And Gastric Myoelectrical Activity, Kenneth L Koch, Henry P Parkman, Katherine P Yates, Mark L Van Natta, Madhusudan Grover, Gianrico Farrugia, Thomas L Abell, Richard W Mccallum, Irene Sarosiek, Braden Kuo, Robert J Shulman, Laura Miriel, James Tonascia, Pankaj J Pasricha

Faculty, Staff and Students Publications

Patients with gastroparesis (Gp) often have diets deficient in calories, electrolytes, and vitamins. Vitamin D levels have been reported to be low in some patients with Gp but has not been systematically studied.

AIMS: To determine vitamin D levels and relationships among symptoms, gastric emptying and gastric myoelectrical activity (GMA) in patients with symptoms of Gp.

METHODS: 25-hydroxy-vitamin D was measured in patients at enrollment in the Gastroparesis Clinical Consortium Registry. Gastroparesis Cardinal Symptoms Index (GCSI), gastric emptying, and GMA before and after water load satiety test (WLST) were measured. GMA, expressed as percentage distribution of activity in normal and …

An Electronic Health Record Model For Predicting Risk Of Hepatic Fibrosis In Primary Care Patients, Aaron P Thrift, Theresa H Nguyen Wenker, Kyler Godwin, Maya Balakrishnan, Hao T Duong, Rohit Loomba, Fasiha Kanwal, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND: One challenge for primary care providers caring for patients with nonalcoholic fatty liver disease is to identify those at the highest risk for clinically significant liver disease.

AIM: To derive a risk stratification tool using variables from structured electronic health record (EHR) data for use in populations which are disproportionately affected with obesity and diabetes.

METHODS: We used data from 344 participants who underwent Fibroscan examination to measure liver fat and liver stiffness measurement [LSM]. Using two approaches, multivariable logistic regression and random forest classification, we assessed risk factors for any hepatic fibrosis (LSM > 7 kPa) and significant hepatic …

Association Of Tea And Coffee Consumption And Biliary Tract Cancer Risk: The Biliary Tract Cancers Pooling Project, Yu-Han Huang, Erikka Loftfield, Ilona Argirion, Hans-Olov Adami, Demetrius Albanes, Andrew T Chan, Veronika Fedirko, Gary E Fraser, Neal D Freedman, Graham G Giles, Patricia Hartge, Verena Katzke, Synnove F Knutsen, James Lacey, Linda M Liao, Juhua Luo, Roger L Milne, Katie M O'Brien, Ulrike Peters, Jenny N Poynter, Mark P Purdue, Kim Robien, Sven Sandin, Dale P Sandler, Veronica W Setiawan, Jae H Kang, Tracey G Simon, Rashmi Sinha, Trang Vopham, Stephanie J Weinstein, Emily White, Xuehong Zhang, Bin Zhu, Katherine A Mcglynn, Peter T Campbell, Mei-Hsuan Lee, Jill Koshiol

Faculty, Staff and Student Publications

Background and aims: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence.

Approach and results: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and < 3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR< 3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers.

Conclusions: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC.

Predicting Mortality Within 1 Year Of Art Initiation In Children And Adolescents Living With Hiv In Sub-Saharan Africa: A Retrospective Observational Cohort Study, Alexander Kay, Bhekumusa Lukhele, Sandile Dlamini, Abigail Seeger, Phumzile Dlamini, Sandile Ndabezitha, Nobuhle Mthethwa, Teresa Steffy, Lilian Komba, Pauline Amuge, Eunice Ketangenyi, Peter Elyanu, Adamson Munthali, Amos Msekandiana, Yvonne Maldonado, Elizabeth Chiao, Adeodata Kekitiinwa, Lineo Thahane, Lumumba Mwita, H Lester Kirchner, Anna Maria Mandalakas

Faculty, Staff and Students Publications

BACKGROUND: Differentiated service delivery (DSD) for children and adolescents living with HIV can improve targeted resource use. We derived a mortality prediction score to guide clinical decision making for children and adolescents living with HIV.

METHODS: Data for this retrospective observational cohort study were evaluated for all children and adolescents living with HIV and initiating antiretroviral therapy (ART); aged 0-19 years; and enrolled at Baylor clinics in Eswatini, Malawi, Lesotho, Tanzania, and Uganda between 2005 and 2020. Data for clinical prediction, including anthropometric values, physical examination, ART, WHO stage, and laboratory tests were captured at ART initiation. Backward stepwise variable …

Gut Development Following Insulin-Like Growth Factor-1 Supplementation To Preterm Pigs, Martin Bo Rasmussen, Kristine Holgersen, Stanislava Pankratova, Ole Bæk, Douglas G Burrin, Thomas Thymann, Per Torp Sangild

Faculty, Staff and Students Publications

BACKGROUND: Reduced insulin-like growth factor-1 (IGF-1) levels may contribute to impaired organ development in preterm infants. Using preterm pigs as a model, we hypothesized that IGF-1 supplementation improves health and gut development during the first three weeks of life.

METHODS: First, clinical and organ endpoints were compared between artificially-reared, cesarean-delivered preterm pigs and vaginally-delivered, sow-reared term pigs at 5, 9 and 19 days. Next, preterm pigs were treated with recombinant human IGF-1 for 19 days (2.25 mg/kg/day, systemically).

RESULTS: Relative to term pigs, preterm pigs had lower body weight, fat, bone contents, relative weights of liver and spleen and a …

Development Of A Follow-Up Measure To Ensure Complete Screening For Colorectal Cancer, Elizabeth L Ciemins, Jeff T Mohl, Carlos A Moreno, Francis Colangelo, Robert A Smith, Mary Barton

Faculty, Staff and Student Publications

IMPORTANCE: The current quality performance measure for colorectal cancer (CRC) screening is limited to initial screening. Despite low rates, there is no measure for appropriate follow-up with colonoscopy after receipt of an abnormal result of a stool-based screening test (SBT) for CRC. A quality performance measure is needed.

OBJECTIVE: To develop and test a quality performance measure for follow-up colonoscopy within 6 months of an abnormal result of an SBT for CRC.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective quality improvement study examined data from January 1, 2016, to December 31, 2020, with 2018 plus 6 months of follow-up as the …

Adverse Metabolic Phenotypes In Parenterally Fed Neonatal Pigs Do Not Persist Into Adolescence, Sarah K Elefson, Barbara Stoll, Teresa A Davis, Marta L Fiorotto, Samer W El-Kadi, Kenneth Genovese, Thomas Thymann, Per T Sangild, Douglas G Burrin

Faculty, Staff and Students Publications

BACKGROUND: Nutrition during fetal and neonatal life is an important determinant for the risk of adult-onset diseases, especially type 2 diabetes and obesity.

OBJECTIVES: We aimed to determine whether total parenteral nutrition (TPN) compared with enteral formula feeding [enteral nutrition (EN)] in term piglets during the first 2 wk after birth would increase the long-term (5-mo) development of metabolic syndrome phenotypes with adverse glucose homeostasis, fatty liver disease, and obesity.

METHODS: Neonatal female pigs were administered TPN (n = 12) or fed enterally with a liquid enteral milk-replacer formula (EN, n = 12) for 14 d. After transitioning TPN pigs …

Protection Against Fibrosis By A Bacterial Consortium In Metabolic Dysfunction-Associated Steatohepatitis And The Role Of Amino Acid Metabolism, Suet-Ying Kwan, Kristyn A Gonzales, Mohamed A Jamal, Heather L Stevenson, Lin Tan, Philip L Lorenzi, P Andrew Futreal, Ernest T Hawk, Joseph B Mccormick, Susan P Fisher-Hoch, Robert R Jenq, Laura Beretta

Faculty, Staff and Student Publications

The gut microbiota drives progression to liver fibrosis, the main determinant of mortality in metabolic dysfunction-associated steatohepatitis (MASH). In this study, we aimed to identify bacterial species associated with protection against liver fibrosis in a high-risk population, and test their potential to protect against liver fibrosis in vivo. Based on stool shotgun metagenomic sequencing of 340 subjects from a population cohort disproportionally affected by MASH, we identified bacterial species from the Bacteroidales and Clostridiales orders associated with reduced risk of liver fibrosis. A bacterial consortium was subsequently tested in a mouse model of MASH, which demonstrated protective effects against …

Recent Trends In The Incidence Of Gastric Cancer In The United States, Kyle S Liu, Syed Ahsan Raza, Hashem B El-Serag, Aaron P Thrift

Faculty, Staff and Students Publications

BACKGROUND: Gastric cancer (GC) incidence rates overall in the United States have declined over recent decades and are predicted to continue declining. However, there have been mixed recent findings regarding the potential stabilization of rates and potential divergent trends by age group. We used the most recent cancer data for the United States and examined trends in GC between 1992 and 2019, overall and in important subgroups of the population.

METHODS: Age-adjusted GC incidence rates and trends in adults 20 years or older were calculated using data from the Surveillance, Epidemiology, and End Results (SEER) 12 program. Secular trends were …

Characterizing Prostate Cancer Risk Through Multi-Ancestry Genome-Wide Discovery Of 187 Novel Risk Variants, Anqi Wang, Jiayi Shen, Alex A Rodriguez, Edward J Saunders, Fei Chen, Rohini Janivara, Burcu F Darst, Xin Sheng, Yili Xu, Alisha J Chou, Sara Benlloch, Tokhir Dadaev, Mark N Brook, Anna Plym, Ali Sahimi, Thomas J Hoffman, Atushi Takahashi, Koichi Matsuda, Yukihide Momozawa, Masashi Fujita, Triin Laisk, Jéssica Figuerêdo, Kenneth Muir, Shuji Ito, Xiaoxi Liu, Yuji Uchio, Michiaki Kubo, Yoichiro Kamatani, Artitaya Lophatananon, Peggy Wan, Caroline Andrews, Adriana Lori, Parichoy P Choudhury, Johanna Schleutker, Teuvo L J Tammela, Csilla Sipeky, Anssi Auvinen, Graham G Giles, Melissa C Southey, Robert J Macinnis, Cezary Cybulski, Dominika Wokolorczyk, Jan Lubinski, Christopher T Rentsch, Kelly Cho, Benjamin H Mcmahon, David E Neal, Jenny L Donovan, Freddie C Hamdy, Richard M Martin, Borge G Nordestgaard, Sune F Nielsen, Maren Weischer, Stig E Bojesen, Andreas Røder, Hein V Stroomberg, Jyotsna Batra, Suzanne Chambers, Lisa Horvath, Judith A Clements, Wayne Tilly, Gail P Risbridger, Henrik Gronberg, Markus Aly, Robert Szulkin, Martin Eklund, Tobias Nordstrom, Nora Pashayan, Alison M Dunning, Maya Ghoussaini, Ruth C Travis, Tim J Key, Elio Riboli, Jong Y Park, Thomas A Sellers, Hui-Yi Lin, Demetrius Albanes, Stephanie Weinstein, Michael B Cook, Lorelei A Mucci, Edward Giovannucci, Sara Lindstrom, Peter Kraft, David J Hunter, Kathryn L Penney, Constance Turman, Catherine M Tangen, Phyllis J Goodman, Ian M Thompson, Robert J Hamilton, Neil E Fleshner, Antonio Finelli, Marie-Élise Parent, Janet L Stanford, Elaine A Ostrander, Stella Koutros, Laura E Beane Freeman, Meir Stampfer, Alicja Wolk, Niclas Håkansson, Gerald L Andriole, Robert N Hoover, Mitchell J Machiela, Karina Dalsgaard Sørensen, Michael Borre, William J Blot, Wei Zheng, Edward D Yeboah, James E Mensah, Yong-Jie Lu, Hong-Wei Zhang, Ninghan Feng, Xueying Mao, Yudong Wu, Shan-Chao Zhao, Zan Sun, Stephen N Thibodeau, Shannon K Mcdonnell, Daniel J Schaid, Catharine M L West, Gill Barnett, Christiane Maier, Thomas Schnoeller, Manuel Luedeke, Adam S Kibel, Bettina F Drake, Olivier Cussenot, Geraldine Cancel-Tassin, Florence Menegaux, Thérèse Truong, Yves Akoli Koudou, Esther M John, Eli Marie Grindedal, Lovise Maehle, Kay-Tee Khaw, Sue A Ingles, Mariana C Stern, Ana Vega, Antonio Gómez-Caamaño, Laura Fachal, Barry S Rosenstein, Sarah L Kerns, Harry Ostrer, Manuel R Teixeira, Paula Paulo, Andreia Brandão, Stephen Watya, Alexander Lubwama, Jeannette T Bensen, Ebonee N Butler, James L Mohler, Jack A Taylor, Manolis Kogevinas, Trinidad Dierssen-Sotos, Gemma Castaño-Vinyals, Lisa Cannon-Albright, Craig C Teerlink, Chad D Huff, Patrick Pilie, Yao Yu, Ryan J Bohlender, Jian Gu, Sara S Strom, Luc Multigner, Pascal Blanchet, Laurent Brureau, Radka Kaneva, Chavdar Slavov, Vanio Mitev, Robin J Leach, Hermann Brenner, Xuechen Chen, Bernd Holleczek, Ben Schöttker, Eric A Klein, Ann W Hsing, Rick A Kittles, Adam B Murphy, Christopher J Logothetis, Jeri Kim, Susan L Neuhausen, Linda Steele, Yuan Chun Ding, William B Isaacs, Barbara Nemesure, Anselm J M Hennis, John Carpten, Hardev Pandha, Agnieszka Michael, Kim De Ruyck, Gert De Meerleer, Piet Ost, Jianfeng Xu, Azad Razack, Jasmine Lim, Soo-Hwang Teo, Lisa F Newcomb, Daniel W Lin, Jay H Fowke, Christine M Neslund-Dudas, Benjamin A Rybicki, Marija Gamulin, Davor Lessel, Tomislav Kulis, Nawaid Usmani, Aswin Abraham, Sandeep Singhal, Matthew Parliament, Frank Claessens, Steven Joniau, Thomas Van Den Broeck, Manuela Gago-Dominguez, Jose Esteban Castelao, Maria Elena Martinez, Samantha Larkin, Paul A Townsend, Claire Aukim-Hastie, William S Bush, Melinda C Aldrich, Dana C Crawford, Shiv Srivastava, Jennifer Cullen, Gyorgy Petrovics, Graham Casey, Ying Wang, Yao Tettey, Joseph Lachance, Wei Tang, Richard B Biritwum, Andrew A Adjei, Evelyn Tay, Ann Truelove, Shelley Niwa, Kosj Yamoah, Koveela Govindasami, Anand P Chokkalingam, Jacob M Keaton, Jacklyn N Hellwege, Peter E Clark, Mohamed Jalloh, Serigne M Gueye, Lamine Niang, Olufemi Ogunbiyi, Olayiwola Shittu, Olukemi Amodu, Akindele O Adebiyi, Oseremen I Aisuodionoe-Shadrach, Hafees O Ajibola, Mustapha A Jamda, Olabode P Oluwole, Maxwell Nwegbu, Ben Adusei, Sunny Mante, Afua Darkwa-Abrahams, Halimatou Diop, Susan M Gundell, Monique J Roobol, Guido Jenster, Ron H N Van Schaik, Jennifer J Hu, Maureen Sanderson, Linda Kachuri, Rohit Varma, Roberta Mckean-Cowdin, Mina Torres, Michael H Preuss, Ruth J F Loos, Matthew Zawistowski, Sebastian Zöllner, Zeyun Lu, Stephen K Van Den Eeden, Douglas F Easton, Stefan Ambs, Todd L Edwards, Reedik Mägi, Timothy R Rebbeck, Lars Fritsche, Stephen J Chanock, Sonja I Berndt, Fredrik Wiklund, Hidewaki Nakagawa, John S Witte, J Michael Gaziano, Amy C Justice, Nick Mancuso, Chikashi Terao, Rosalind A Eeles, Zsofia Kote-Jarai, Ravi K Madduri, David V Conti, Christopher A Haiman

Faculty, Staff and Student Publications

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in …

Estradiol Mediates Colonic Epithelial Protection In Aged Mice After Stroke And Is Associated With Shifts In The Gut Microbiome, Juneyoung Lee, Pedram Peesh, Victoria Quaicoe, Chunfeng Tan, Anik Banerjee, Patrick Mooz, Bhanu P Ganesh, Joseph Petrosino, Robert M Bryan, Louise D Mccullough, Venugopal Reddy Venna

Faculty, Staff and Student Publications

The gut is a major source of bacteria and antigens that contribute to neuroinflammation after brain injury. Colonic epithelial cells (ECs) are responsible for secreting major cellular components of the innate defense system, including antimicrobial proteins (AMP) and mucins. These cells serve as a critical regulator of gut barrier function and maintain host-microbe homeostasis. In this study, we determined post-stroke host defense responses at the colonic epithelial surface in mice. We then tested if the enhancement of these epithelial protective mechanisms is beneficial in young and aged mice after stroke. AMPs were significantly increased in the colonic ECs of young …

Incidence And Outcomes Of Acute Kidney Injury Including Hepatorenal Syndrome In Hospitalized Patients With Cirrhosis In The Us, Kavish R Patidar, Justin M Belcher, Kevin R Regner, Shelsea A St Hillien, Douglas A Simonetto, Sumeet K Asrani, Javier A Neyra, Pratima Sharma, Juan Carlos Q Velez, Hani Wadei, Mitra K Nadim, Raymond T Chung, Ritu Seethapathy, Xavier Vela Parada, Tianqi Ouyang, Nneka N Ufere, Jevon E Robinson, Paige Mclean Diaz, Robert M Wilechansky, Eric M Przybyszewski, Thomas N Smith, Arzina Aziz Ali, Eric S Orman, Philipp Schulz, Salaah M Siddiqui, Rehma Shabbir, Lucas J Liu, Augusto Cama-Olivares, Alexander H Flannery, Megan L Baker, Deepthi Gunasekaran, Adeline Aswine, Rafik Issa, Jay Li, Shreya Verma, Dustin Chalmers, Vipin Varghese, Walter Lam, Muner Mohamed, Rosemary Kovacic, Anna Gaddy, Rose Mary Attieh, Pedro Cortes, Sahar Semnani, Lin Wang, Saro Khemichian, Andrew S Allegretti

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Acute kidney injury (AKI) in cirrhosis is common and associated with high morbidity, but the incidence rates of different etiologies of AKI are not well described in the US. We compared incidence rates, practice patterns, and outcomes across etiologies of AKI in cirrhosis.

METHODS: We performed a retrospective cohort study of 11 hospital networks, including consecutive adult patients admitted with AKI and cirrhosis in 2019. The etiology of AKI was adjudicated based on pre-specified clinical definitions (prerenal/hypovolemic AKI, hepatorenal syndrome [HRS-AKI], acute tubular necrosis [ATN], other).

RESULTS: A total of 2,063 patients were included (median age 62 …